CN103645319A - Application of macrophage inhibiting factor-1 in colorectal cancer diagnosis - Google Patents
Application of macrophage inhibiting factor-1 in colorectal cancer diagnosis Download PDFInfo
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- G01N33/57488—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites involving compounds identifable in body fluids
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Abstract
The invention relates to an application of a macrophage inhibiting factor-1 in colorectal cancer diagnosis, and in particular relates to an application of a tumor marker in preparation of a reagent or a kit for diagnosing and/or monitoring colorectal cancer of a subject, wherein the tumor marker comprises the macrophage inhibiting factor-1 and a TPS. The invention further relates to the reagent or the kit for diagnosing and/or monitoring colorectal cancer of the subject, and the reagent or the kit comprises a reagent for detecting the tumor marker. The tumor market provided by the invention has good complementarity, can greatly improve the detection efficiency of colorectal cancer, and has a good application prospect.
Description
Technical field
The present invention relates to diagnosis of colorectal carcinoma monitoring field.Particularly, the present invention relates to the application of macrophage inhibition factor 1 in diagnosis of colorectal carcinoma and monitoring, relate in particular to other tumor markers of macrophage inhibition factor 1 associating if MIC-1, CEA, TPS are in the particularly application in early stage diagnosis of colorectal carcinoma of colorectal cancer.
Background technology
Colorectal cancer comprises colon cancer and the carcinoma of the rectum, and mortality ratio occupies the 4th in China city, in rural area, occupies the 5th.In PATIENTS WITH LARGE BOWEL, mostly there is no in early days obvious clinical symptoms and sign, once find to be middle and advanced stage, in China, the incidence of disease of colorectal cancer has obvious ascendant trend, is that of human health threatens greatly.The early detection of colorectal cancer can effectively reduce the mortality ratio of intestinal cancer, thereby the early diagnosis of colorectal cancer research becomes the focus in intestinal cancer research.
There is no at present the tumor markers of desirable diagnosis colorectal cancer, clinical detection be take carcinomebryonic antigen (CEA) and carbohydrate antigen (CA) as main.CEA is the colorectal cancer blood serum tumor markers of finding the earliest, molecular weight is about the glycoprotein of 180kD, encoding gene is positioned at chromosome No. 19, CEA all has rising in various degree in most of malignant tumour serum, often be used as clinically the auxiliary diagnostic index of malignant tumor of digestive tract, but the susceptibility of its detection and specificity all can not meet the demand of clinical detection, the positive rate of preoperative CEA is greatly between 30%-40%.On the cell membrane of the main expression of CA series and canceration, also can be discharged in cytoplasm matter, thereby can be used for diagnosis and the treatment monitoring of tumour, what be usually used at present diagnosis of colorectal carcinoma has CA199, CA125, CA242 and a CA724, research finds that size, Bormann somatotype, lymphatic infiltration and the histological type of CA series antigen and tumour exist correlativity, in the diagnosis of colorectal cancer and treatment, there is important value, but there is too the poor problem of susceptibility and specificity, the diagnostic sensitivity less than 30% of single CA mark.A large sample clinical research result demonstration, the preoperative CEA positive rate of patients with bowel cancer is that 32.6%, CA199 positive rate is 25.0%.The positive rate of CEA and CA199 joint-detection is 44.2%, though illustrate that the positive rate of joint-detection is high compared with individual event mensuration, little to the diagnostic value of the carcinoma of the rectum.
Value of tissue polypeptide specific antigen (Tissue Polypeptide Specific antigen, TPS) is a kind of polypeptide antigen of tumor cell secretion, is to report in recent years a more tumor markers for malignant tumor of digestive tract diagnosis.TPS concentration increases relevant with tumour epithelial cell proliferation activity of conversion, is the specific parameters of reflection tumour cell division and proliferation activity, belongs to tumor promotion dependent form label.There are some researches show, TPS can effectively monitor curative effect in FOL-FIRI Regimen Chemotherapy colorectal cancer, and treatment responder TPS level significantly declines, disease progression person significantly raise, and its susceptibility is high, the time of variation early, can be reacted change of illness state quickly than CEA, CA.For advanced colorectal cancer, to diagnose clearly, it is more conducive to the monitoring to treatment, and the variation of dynamically observing serum T PS level can be used as an index evaluating treatment of colorectal cancer effect.
Even if large quantity research shows associating CEA, TPA and CA series, the sensitivity of its diagnosis colorectal cancer is less than 60% still, and clinical meaning is limited, and particularly not enough, three combines the sensitivity less than 30% of early stage (I+II phase) colorectal cancer of diagnosis.The early detection that improves patients with bowel cancer and treatment are the effective ways that reduces intestinal cancer mortality ratio, and for this reason, the tumor markers that exploration discovery can be used in early diagnosis intestinal cancer becomes an important task.
Summary of the invention
Digital proof MIC-1 serum reagent box of the present invention has shown good application prospect in diagnosis of colorectal carcinoma research.Digital proof MIC-1 of the present invention is better than CEA in intestinal cancer diagnosis in early days, in patients with bowel cancer group and Normal group serum MIC-1 level, has significant difference (P < 0.001).In early days in patients with bowel cancer, the diagnostic sensitivity of MIC-1 (the I phase: 22.7%; The II phase: 34.7%) all higher than the susceptibility of CEA, CA199, each tumor markers of TPS.
The diagnosis of combining of tumor markers at present is also more and more widely used in clinical.Yet, for cost-saving, shorten detection time, reduce many-sided considerations such as experimental error, combine in diagnosis and especially need to consider that the minimum mark of associating obtains sufficiently high susceptibility and specificity.Due to the compatibility between various tumor markerses, the simple combination of existing mark is difficult to obtain gratifying effect, and how obtain from known numerous tumor markers, can significantly improve susceptibility and specific 2-3 kind mark and realize efficient diagnosis and be very difficult to expection, become the problem that this area is furtherd investigate.Inventor finds that MIC-1 and CEA, TPS have good incompatibility surprisingly, in the middle of patient, MIC-1 and TPS present positive result simultaneously and only have a very little part, the positive rate of MIC-1+TPS can reach 57.8%, and the positive rate that MIC-1+CEA+TPS is combined in colorectal cancer detection can bring up to 72.5% especially.More it is shocking, the susceptibility that in (I phase+II phase) intestinal cancer, MIC-1, CEA, TPS three combine diagnosis in early days can reach 61.3%, with add CA199 after four to combine the susceptibility of diagnosis equally matched, in the patients with bowel cancer serum of III phase+IV phase, also have similar result.In addition, inventor finds to use other marks (CA125, CA242, CA724) of CA series to replace CA199, and result is similar, all fails to improve the sensitivity of diagnosis.Therefore, result of the present invention shows only to combine MIC-1+TPS, and the two can significantly improve the positive rate of diagnosis, associating MIC-1, CEA, TPS three can obtain gratifying effect, further combine CA199 or other CA marks can not significantly improve positive rate.
Therefore, one aspect of the present invention relates to the reagent of tumor markers colorectal cancer in preparation diagnosis and/or monitoring experimenter or the purposes in kit, wherein said tumor markers comprise macrophage inhibition factor 1 and TPS the two.
In one embodiment of the invention, described tumor markers does not comprise that CA mark is as CA199, CA125, CA242 and CA724.
In one embodiment of the invention, described tumor markers comprises macrophage inhibition factor 1, TPS and CEA.
In one embodiment of the invention, described tumor markers is comprised of macrophage inhibition factor 1 and TPS.Proved that MIC-1 and TPS present positive result simultaneously and only have a very little part, used the positive rate of the two associating of MIC-1+TPS can be up to 57.8%, and known combination as the Positive rate of CEA and CA199 be only 44.2%.
In another embodiment of the invention, described tumor markers is comprised of macrophage inhibition factor 1, TPS and CEA.Proved that MIC-1 and CEA, TPS have good incompatibility, MIC-1+CEA+TPS is combined in the positive rate of colorectal cancer in detecting up to 72.5%.Inventor finds that MIC-1+CEA+TPS three is especially suitable for combining early stage (I+II phase) colorectal cancer of diagnosis surprisingly, and susceptibility can reach 61.3%, and the sensitivity less than 30% of the sign joint-detection of existing report.More it is shocking, inventor finds, except MIC-1+CEA+TPS combination, further to use the mark of CA series as CA199, CA125, and CA242, CA724 fails to significantly improve the sensitivity of diagnosis.Therefore, only combining MIC-1, CEA, TPS three can obtain gratifying effect, and when diagnosing early stage colorectal cancer, this is very astonishing.Therefore, in a preferred embodiment of the invention, the tumor markers using does not comprise that CA mark is as CA199, CA125, CA242 and CA724 etc.
In one embodiment of the invention, described colorectal cancer is early stage colorectal cancer.
In one embodiment of the invention, described colorectal cancer is I phase and/or II phase colorectal cancer.
In one embodiment of the invention, described reagent or kit for T by stages and/or M by stages.
In one embodiment of the invention, reagent of the present invention or kit can be used for the expression (for example mRNA level) that tissue in situ detected and/or monitored described tumor markers, or for detection of and/or monitor the serum levels of described tumor markers.
The opposing party of the present invention aspect relates to reagent or the kit of colorectal cancer in diagnosis and/or monitoring experimenter, comprising above-described reagent or kit.In the present invention, find that the combination of tumor markers can be used for after the detection or monitoring of colorectal cancer, such reagent and/or kit can easily be prepared by this area routine techniques.For example described reagent and/or kit can comprise the antibody that detects described tumor markers, preferred monoclonal antibody, or the primer of expressing for detection of described tumor markers and/or probe etc.Described reagent or kit can also comprise the conventional damping fluid that carries out PCR reaction, polymerase, dNTPs potpourri etc.Kit of the present invention can also comprise operation instructions etc.
Accompanying drawing explanation
Fig. 1: MIC-1, the CA199, CEA and the TPS level that detect collected serum sample, and the ROC curve (because not obtaining and contrasting corresponding TPS numerical value, so ROC curve does not comprise TPS) of drawing with MIC-1, the CA199 of Normal group and the concentration of CEA with this sample.
Embodiment
1 materials and methods
1.1 medical history information
All cases are all from October, 2009 to 2011 year Cancer Hospital of Chinese Academy of Medical Sciences outpatient service in January and inpatient (in Table 1) case group 429 examples, 58.6 years old mean age, the median age 59.0 years old, normal control 129 examples, 43.3 years old mean age, the male sex's 75 examples, women's 54 examples, age 20-80 year, 43.3 years old mean age, the median age 44.0 years old, normal control is from Cancer Hospital of Chinese Academy of Medical Sciences people taking physical examination, all, without digestive system illness, hepatic and renal function is normal.
Table 1: patient clinical pathological characters
1.2 detection method
1.2.1 the collection of blood serum sample adopts the import vacuum test tube (reddish tone pipe) with inertia separation gel to extract respectively patient's limosis vein blood 4ml; Nature aggegation 30min, 8 ℃, the centrifugal 15min separation of serum of 4000rpm; Also-80 ℃ of low temperature refrigerators of packing are preserved to be measured.MIC-1, CA199, CEA, TPS critical reference value are respectively 1000pg/ml, 37U/ml, 5ng/ml and 110U/L, and when its critical reference value, specificity is all in 97% left and right.In combining diagnosis, adopt series connection associating diagnosis, in all tumor markerses, have a positive just to judge that assay is positive, improve the susceptibility of diagnosis.
1.2.2MIC-1 it is Cancer Hospital of Chinese Academy of Medical Sciences research and development that detection method MIC-1 detects kit used, adopt the ELISA double-antibody sandwich two-step approach of biotin-avidin amplification system, with Bole imark microplate reader, 450nm, 655nm dual wavelength detect each hole OD value, and operation is carried out in strict accordance with instrument and reagent operation instructions.
1.2.3CA199, the detection method of CEA, TPS all adopts Roche Cobas601 electrochemiluminescence immunity analysis instrument and matched reagent box (Roche) to detect, operation is carried out in strict accordance with instrument and reagent operation instructions, and high and low Quality Control performance number is all in claimed range.
1.3 statistical procedures
In serum, MIC-1 concentration represents with means standard deviation and median.Application SPSS18.0 software carries out statistical study, and Mann-Whitney U test analyzes the MIC-1 level of respectively organizing, ROC tracing analysis MIC-1 and detects usefulness and determine that its critical value, Chi-Square Test detect MIC-1 in the difference detection sensitivity in colorectal cancer by stages.Statistical test is two-sided test, and P < 0.05 has statistical significance for difference.
2. result
2.1ROC curve
Detect MIC-1, CA199, CEA and the TPS level of collected serum sample, and with MIC-1, the CA199 of this sample and Normal group and the concentration of CEA, draw ROC curve and (see Fig. 1, because not obtaining and contrasting corresponding TPS numerical value, so ROC curve does not comprise TPS).Result shows that the AUC of MIC-1 is 0.803, higher than CA199 (0.762) and CEA (0.697).Considered 2 times of standard deviations of MIC-1 mean value ± and ROC curve in normal population, the critical value of establishing MIC-1 is 1000pg/ml.When specificity is 96.9, the susceptibility of MIC-1 is 35.2%.
MIC-1 level in 2.2 patients with bowel cancers and normal control serum
Detect respectively the MIC-1 level in patients with bowel cancer and normal control serum, found that in patients with bowel cancer serum, MIC-1 concentration is significantly higher than Normal group (P < 0.001) (table 2)
Table 2: patients with bowel cancer and the horizontal table of comparisons of normal control serum MIC-1
The AUC of MIC-1, CA199, CEA and diagnostic value in 2.3 intestinal cancer
Known according to testing result and ROC curve, the AUC value of MIC-1 is 0.803, higher than present CEA (0.697) and CA199 (0.762) for clinical detection, when specificity is 97% left and right, the detection sensitivity of MIC-1 is 35.2% suitable with CEA, and is significantly higher than CA199 (Fig. 1, table 3)
Table 3: AUC value and the diagnostic value of MIC-1, CA199, CEA and TPS in patients with bowel cancer
2.4MIC-1 and TNM relation by stages
According to Analysis of test results MIC-1 level respectively with T by stages, N by stages, M relation by stages, result shows that the concentration of MIC-1 in serum raises (P < 0.05) with T stage development and detection sensitivity raises with T stage development, and statistics has statistical significance (P=0.016); The concentration of MIC-1 in serum is at N0 and N1 is interim a significant difference (P=0.033), at N1 and N2, N2 and N3 is interim there is no significant difference (P > 0.05), and detection sensitivity no difference of science of statistics (P=0.146) in different N intestinal cancer by stages; The level of MIC-1 in serum has extremely significant difference (P < 0.001) in M0 and M1 phase colorectal cancer, and its detection sensitivity also has significant difference in the statistics of different M phase intestinal cancer, and with development by stages raise (P=0.002) (table 4)
Table 4:MIC-I and T by stages, N by stages, M relation by stages
Remarks: P
1for MIC-1 is at the difference result that the concentration level U in Serum In Patients With Colorectal Carcinoma detects, P by stages
2for the Chi-Square assay a of MIC-1 detection sensitivity is Pearson Chi-Square; B is Fisher ' s Exact Test; C is Continuity Correction (a)
The relation of 2.5MIC-1 and differentiation
This experimental analysis the MIC-1 level in the intestinal cancer patients serum of different differentiation degrees, in high, medium and low differentiation intestinal cancer, the susceptibility of MIC-1 does not have significant difference (P=0.404), but the serum levels of the PATIENTS WITH LARGE BOWEL of different differentiation degrees is different, differentiated large with middle differentiation Serum In Patients With Colorectal Carcinoma in, MIC-1 level does not have significant difference (P=0.319), but in middle differentiation and low differentiation Serum In Patients With Colorectal Carcinoma, MIC-1 concentration level has significant difference (P=0.044)
The relation of table 5:MIC-1 detection sensitivity and different differentiation degree intestinal cancer
Remarks: P
1for the result that the concentration level U of MIC-1 in different differentiation degree Serum In Patients With Colorectal Carcinomas detects, P
2for the Chi-Square assay a of MIC-1 detection sensitivity is Pearson Chi-Square
2.6MIC-1, CA199, CEA, TPS are in the difference susceptibility in intestinal cancer by stages
The MIC-1 in early days susceptibility in intestinal cancer (I phase+II phase) is respectively 22.7%, 6.8%, 13.6% and 13.6% higher than the susceptibility of four kinds of marks in CA199, CEA, TPS:I phase patients with bowel cancer: in II phase patients with bowel cancer, the susceptibility of these four kinds of tumor markerses is respectively 34.7%, 11.3%, 29.8% and 29.0.MIC-1 in the interim susceptibility of I～IV in Table 6.
Table 6:MIC-1, CA199, CEA, TPS are in the difference susceptibility in intestinal cancer by stages
2.7MIC-1, CA199, CEA, TPS combine diagnosis
Tumor markers combine the susceptibility that diagnosis can significantly improve diagnosis, this experiment has been chosen MIC-1 and has been combined diagnosis (table 7) with conventional intestinal cancer detection mark CA199, CEA and TPS, result shows that MIC-1 combines diagnosis and can obtain good susceptibility with CEA, tri-kinds of tumor markerses of TPS, especially in early days in intestinal cancer, the diagnostic sensitivity of MIC-1+CEA+TPS can reach 61.3%.Analyzing and testing found that, MIC-1 and CEA, TPS have good incompatibility, in the middle of patient, MIC-1 and CEA or MIC-1 and TPS present positive result simultaneously and only have a very little part, thereby combine the detector efficiency that this detection index can significantly improve colorectal cancer.The positive rate that the positive rate of MIC-1+CEA can reach 62.7%, MIC-1+TPS can reach 57.8%, and the positive rate that MIC-1+CEA+TPS is combined in colorectal cancer detection can bring up to 72.5% especially.Especially MIC-1+TPS, MIC-1+CEA+TPS combination, there is no at present the report that this combination detects for colorectal cancer, and this research is also unexpected, find that MIC-1, CEA, TPS three have good complementarity in colorectal cancer serum detects, and have good application prospect.
Table 7: tumor markers is combined the positive rate (%) of diagnosis
3. discuss
Colorectal cancer is one of malignant tumour of serious threat human health, and China's colorectal cancer mortality ratio occupies the 4th in city in recent years, in rural area, occupies the 5th, and M & M journey ascendant trend year by year.Research shows that postoperative 5 years survival rates of early stage colorectal cancer can reach 97%, and 5 years survival rates of advanced colorectal cancer only 40% one 50%, thereby the early detection that improves patients with bowel cancer and treatment be the effective way that reduces intestinal cancer mortality ratio, the tumor markers that exploration discovery can be used in early diagnosis becomes an important task.
GDF-15 (MIC-1) [1,2] is the tumor markers of a wide spectrum in recent years finding, as the member of TGF-'beta ' family, and the biological processes such as wide participation Apoptosis, metastasis.Ripe MIC-1 albumen in normal human serum is low-level stably express, under pathological state, as its expression of tumour, acute injury and inflammation can be one, crosses property significantly raise [3,4].Multinomial research shows in polytype Serum of Cancer Patients, all have MIC-1 expression in various degree to raise, and especially in some infantile tumour patients serums, MIC-1 level can be used as the generation that a good mark is pointed out tumour.
Foreign study finds that body serum MIC-1 level and body are proportionate to the pernicious transition process of far-end transfer from normal, adenoma, cancer, is progressively ascendant trend and difference and has statistical significance (P < 0.05) [5].High serum MIC-1 is often indicating that the possibility of DISTANT METASTASES IN and recurrence increases and the shortening [5,7] of life cycle.
A large amount of research work have been done in this laboratory also double-antibody sandwich elisa serum MIC-1 detection kit based on independent research, research finds that in early days in Pancreas cancer patients, diagnostic sensitivity can reach 77.9%[8], in the diagnosis of cancer of the stomach and lung cancer, also demonstrate good prospect in early days, be better than current other tumor markers [9,10] for cancer of the stomach and pulmonary cancer diagnosis.In this research, find, although total susceptibility and the CEA of MIC-1 are similar, but MIC-1 is better than CEA in intestinal cancer diagnosis in early days, in patients with bowel cancer group and Normal group serum MIC-1 level, there is significant difference (P < 0.001), and in patients with bowel cancer, with development by stages of TNM, progressively raise, its detection sensitivity is the (T:P=0.016 that is proportionate of development by stages with M by stages with T also; M:P=0.002) no difference of science of statistics (P=0.146) and in different N patient by stages.
This research is also analyzed the intestinal cancer serum MIC-1 of different differentiation degrees, find that the susceptibility that in the intestinal cancer serum of different differentiation degrees, MIC-1 detects does not have significant difference (P=0.404), point out our MIC-1 gene in the intestinal cancer of different differentiation degrees, all to have expression activation in various degree.In early days in patients with bowel cancer, the diagnostic sensitivity of MIC-1 (the I phase: 22.7%; The II phase: the susceptibility of 34.7%) all diagnosing separately higher than CEA, CA199, each tumor markers of TPS, this result is consistent with the discovery of this laboratory in early-stage Study.
Because single markers in diagnosis is often difficult to meet the needs of clinical detection, at present tumor markers combine diagnosis be also more and more widely used in clinical, tumor markers combine the development trend that diagnosis is also early diagnosis of cancer.Not yet find that there is at present MIC-1+TPS, MIC-1+CEA+TPS applied in any combination in the report of colorectal cancer detection, in this research, find MIC-1, CEA, TPS in intestinal cancer detects, be can be complementary tumor markers, this combination can significantly improve colorectal cancer and detect the susceptibility that especially early stage colorectal cancer detects.In (I phase+II phase) intestinal cancer, the susceptibility of MIC-1, CEA, TPS is respectively 31.5%, 25.6% and 25.0% in early days, but combining the susceptibility of diagnosis, three can reach 61.3%, with add CA199 after four to combine diagnosis 62.5% susceptibility equally matched, and be significantly higher than each mark susceptibility of diagnosis separately.In the patients with bowel cancer serum of III phase+IV phase, also there is similar result (79.7%vs80.8%).This result of study provides theoretical foundation for the further liquid phase suspending chip multi-tumor marker detection kit of exploitation based on xMAP technology, this technology can further improve clinical detection susceptibility, use manpower and material resources sparingly.
In sum, MIC-1, as a sensibility tumor mark of intestinal cancer early diagnosis, has very important clinical value.And MIC-1 combines the diagnosis that diagnosis can significantly improve early stage intestinal cancer with CEA, TPS three, also tool has very important clinical value.
List of references:
1.Bootcov，M.R.，et?al.，MIC-1，a?novel?macrophage?inhibitory?cytokine，is?a?divergent?member?of?the?TGF-beta?superfamily.Proc?Natl?Acad?Sci?U?S?A，1997.94(21)：p.11514-9.
2.Unsicker，K.，B.Spittau?and?K.Krieglstein，The?multiple?facets?of?the?TGF-beta?family?cytokine?growth/differentiation?factor-15/macrophage?inhibitory?cytokine-1.Cytokine?Growth?Factor?Rev，2013.
3.Bauskin，A.R.，et?al.，Role?of?macrophage?inhibitory?cytokine-1in?tumorigenesis?and?diagnosis?of?cancer.Cancer?Res，2006.66(10)：p.4983-6.
4.Khaled，Y.S.，E.Elkord?and?B.J.Ammori，Macrophage?inhibitory?cytokine-1：a?review?of?its?pleiotropic?actions?in?cancer.Cancer?Biomark，2012.11(5)：p.183-90.
5.Brown，D.A.，et?al.，MIC-1serum?level?and?genotype：associations?with?progress?and?prognosis?of?colorectal?carcinoma.Clin?Cancer?Res，2003.9(7)：p.2642-50.
6.Xue，H.，et?al.，Identification?of?serum?biomarkers?for?colorectal?cancer?metastasis?using?a?differential?secretome?approach.J?Proteome?Res，2010.9(1)：p.545-55.
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8. king dogface, et al., the large sample clinical research of GDF-15 in Pancreas cancer patients serum. cancer progression, 2011.9 (4): p.367-373.
9. king dogface, et al., the clinical value research of GDF-15 in Serum Obtained From Advance Gastric Cancer. cancer progression, 2011.9 (4): p.379-383.
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Claims (10)
1. the reagent of tumor markers colorectal cancer in preparation diagnosis and/or monitoring experimenter or the purposes in kit, wherein said tumor markers comprise macrophage inhibition factor 1 and TPS the two.
2. purposes claimed in claim 1, wherein said tumor markers does not comprise that CA mark is as CA199, CA125, CA242 and CA724.
3. purposes claimed in claim 1, wherein said tumor markers comprises macrophage inhibition factor 1, TPS and CEA.
4. the purposes described in claim 1 or 2, wherein said tumor markers is comprised of macrophage inhibition factor 1 and TPS.
5. the purposes described in any one in claim 1-3, wherein said tumor markers is comprised of macrophage inhibition factor 1, TPS and CEA.
6. the purposes described in any one in claim 1-5, wherein said colorectal cancer is early stage colorectal cancer.
7. the purposes described in any one in claim 1-6, wherein said colorectal cancer is I phase and/or II phase colorectal cancer.
8. the purposes described in any one in claim 1-7, wherein said reagent or kit for T by stages and/or M by stages.
9. the purposes described in any one in claim 1-8, wherein said reagent or kit for detection of and/or the serum levels of monitoring macrophage inhibition factor 1.
10. diagnose and/or monitor reagent or the kit of colorectal cancer in experimenter, wherein said reagent or kit comprise reagent or the kit defining in any one in claim 1-9.
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| GB2551415A (en) * | 2016-10-07 | 2017-12-20 | Applied Proteomics Inc | Protein biomarker panels for detecting colorectal cancer and advanced adenoma |
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| CN103913575A (en) * | 2013-05-07 | 2014-07-09 | 上海良润生物医药科技有限公司 | Combined application of cystatin S and carbohydrate antigen 19-9 |
| CN103913575B (en) * | 2013-05-07 | 2016-02-10 | 上海良润生物医药科技有限公司 | The use in conjunction of CST4 and CA19-9 |
| GB2551415A (en) * | 2016-10-07 | 2017-12-20 | Applied Proteomics Inc | Protein biomarker panels for detecting colorectal cancer and advanced adenoma |
| GB2551415B (en) * | 2016-10-07 | 2018-07-04 | Applied Proteomics Inc | Methods of assessing colorectal health of an individual |
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